Our studies this year indicate that the gp appears to be unable to control cholesterol pool expansion by limiting intestinal absorption. The methods used in this study require further validation because they had not previously been used in the gp. By the use of immunodiffusion and immunoelectrophoresis of antisera against purified apolipoproteins of control and cholesterol-fed guinea pigs we have found evidence that apolipoproteins of chol-fed guinea pigs contain an antigenic determinant that is undetectable in those of controls. More sensitive methods, like radioimmune assay will be used to confirm these findings. Amino acid determinations of the polypeptide constituents of guinea pig apo-HDL has shown that apo-HDL of cholesterol-fed guinea pigs contains a polypeptide that resembles the "arginine-rich" polypeptide observed in certain human lipid abnormalities. Further characterization of these polypeptides is under way. We have found that the "spicule" formation of guinea pig RBC in response to dietary cholesterol is associated with increases of the membrane ATP-ase and pyruvate kinase activities. This may indicate a more rapid turnover and/or a greater requirement for ATP. This in turn may be related to an increased energy demand for cation transport across the more viscous, cholesterol-loaded membrane. Further studies of the energy metabolism of these membranes and their cation transport with emphasis of Ca ions will be undertaken.